Project Summary/Abstract: The candidate's long-term career goal is to become an independent investigator with transdisciplinary expertise in cancer epidemiology, biomedical informatics, pharmacoepidemiology, and health economic modeling and evaluation. The focused didactic training, mentorship, and experiential learning through research activities proposed in this award will facilitate the development of critical skills in the pursuit of knowledge to inform and improve cancer prevention and screening. The candidate's research is motivated by the recognition that type-2 diabetes mellitus (T2DM) patients are at a 30-40% increased risk for colorectal cancer (CRC), and that anti-diabetic drugs may also alter CRC risk. Thus, this high-risk group presents an opportunity for targeted screening and early detection of CRC. Currently, CRC screening is based on age and family history, with no consideration for comorbidities, including T2DM. Building on her previous work in cancer epidemiology, the candidate seeks to determine the association between T2DM and risk of colorectal polyps: overall, by subtypes, and by lesion severity, individually reflecting different molecular pathways (Aim 1); and to examine the risk for colorectal polyps associated with anti-diabetic therapy: overall, by subtypes, and by lesion severity (Aim 2). These aims will be addressed by leveraging the rich resources of an existing colonoscopy- based cohort at the University of Washington Medical Center's (UWMC) Gastroenterology clinic established during 2003-2011. Demographics, select lifestyle factors, and detailed histopathology have been previously abstracted from UWMC's electronic medical records (EMR) database. The candidate proposes to extend this cohort through 2017 (N~38,000), and enhance it by linking existing data with diabetes-related variables from the EMR database using biomedical informatics (e.g., natural language processing, clinical text mining) to estimate the risk for colorectal neoplasia. Using these empirical estimates derived from Aims 1 and 2, the candidate will then build a microsimulation model projecting the risk for colorectal neoplasia in T2DM patients, accounting for their diabetes therapy. Alternative screening and treatment strategies, including altering the screening start-age, modifying diabetes treatment, or altering screening modality among T2DM patients, will be evaluated for their cost-effectiveness (Aim 3). This work may help inform targeted screening recommendations that could, in turn, lower the incidence and mortality of CRC among persons with T2DM, and improve the cost- effectiveness of CRC screening. The candidate has proposed a training and career development plan that builds upon her prior skills in cancer epidemiology to gain experience and proficiency in biomedical informatics, pharmacoepidemiology, and health economic modeling and evaluation, including cost-effectiveness approaches. The transdisciplinary mentorship team, comprised of national and international experts, will provide the necessary expertise to ensure the success of this proposal, as well as facilitate the candidate's transition into an independent translational investigator in the field of cancer prevention and screening.